Angiotensin II type 1 receptor blockers as a first choice in patients with acute myocardial infarction

BACKGROUND/AIMS: Angiotensin II type 1 receptor blockers (ARBs) have not been adequately evaluated in patients without left ventricular (LV) dysfunction or heart failure after acute myocardial infarction (AMI). METHODS: Between November 2005 and January 2008, 6,781 patients who were not receiving angiotensin-converting enzyme inhibitors (ACEIs) or ARBs were selected from the Korean AMI Registry. The primary endpoints were 12-month major adverse cardiac events (MACEs) including death and recurrent AMI. RESULTS: Seventy percent of the patients were Killip class 1 and had a LV ejection fraction > or = 40%. The prescription rate of ARBs was 12.2%. For each patient, a propensity score, indicating the likelihood of using ARBs during hospitalization or at discharge, was calculated using a non-parsimonious multivariable logistic regression model, and was used to match the patients 1:4, yielding 715 ARB users versus 2,860 ACEI users. The effect of ARBs on in-hospital mortality and 12-month MACE occurrence was assessed using matched logistic and Cox regression models. Compared with ACEIs, ARBs significantly reduced in-hospital mortality(1.3% vs. 3.3%; hazard ratio [HR], 0.379; 95% confidence interval [CI], 0.190 to0.756; p = 0.006) and 12-month MACE occurrence (4.6% vs. 6.9%; HR, 0.661; 95% CI, 0.457 to 0.956; p = 0.028). However, the benefit of ARBs on 12-month mortality compared with ACEIs was marginal (4.3% vs. 6.2%; HR, 0.684; 95% CI, 0.467 to 1.002; p = 0.051). CONCLUSIONS: Our results suggest that ARBs are not inferior to, and may actually be better than ACEIs in Korean patients with AMI.

Human fetal malformations associated with the use of an angiotensin II receptor antagonist: Case Report / Malformações fetais associadas ao uso de antagonista dos receptores de angiotensina II: Relato de Caso

Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant. .

Introdução: Os riscos relacionados à exposição de drogas durante a gestação representam um vasto capítulo na obstetrícia moderna e dados sobre a segurança de drogas anti-hipertensivas são relativamente escassos. Relato do caso: Paciente de 37 anos, hipertensa crônica, descobriu a gravidez com 26 semanas e 4 dias de gestação. Estava em uso regular de Losartana. Durante avaliação fetal ultrassonográfica, foi relatada a presença de grave oligoâmnio associado ao quadro de centralização fetal com alteração de ducto venoso, e, após 36 horas, verificou-se óbito neonatal. Necrópsia: Observou-se calota craniana com fontanelas amplas e ossificação deficiente. Rins levemente aumentados de volume e, à microscopia, hipodesenvolvimento de túbulos com presença de lúmen dilatado. Imunohistoquímica com expressão em túbulos distais de antígeno epitelial de membrana. Imunoperoxidade com expressão em túbulos proximais de CD 15 em células epiteliais e colapso de alguns lúmens fora observado. Discussão: Inibidores da conversão de angiotensina e antagonistas de receptor de angiotensina estão entre as drogas mais prescritas para hipertensão. Estas drogas são frequentemente prescritas para mulheres em idade fértil e que pretendem engravidar. Enquanto a toxicidade fetal destas, nos segundo e terceiro trimestres, já é conhecida, seus efeitos durante o primeiro trimestre foi apenas recentemente demostrado. Conclusão: A conscientização por parte de médicos e pacientes deve ser realizada de rotina, principalmente no que diz respeito à prescrição e utilização de drogas potencialmente teratogênicas ou fetotóxicas. Este cuidado deve ser redobrado para pacientes que estão ...

Effect of renin-angiotensin-system blockers on contrast-medium-induced acute kidney injury after coronary angiography

BACKGROUND/AIMS: With the increasing incidence of cardiovascular disease, angiocardiography using contrast-enhancing media has become an essential diagnostic and therapeutic tool, despite the risk of contrast-medium-induced acute kidney injury (CIAKI). CIAKI may be exacerbated by renin-angiotensin-system (RAS) blockers, which are also used in a variety of cardiovascular disorders. This study evaluated the effects of RAS blockade on CIAKI after coronary angiography. METHODS: Patients who underwent coronary angiography in our hospital between May 2009 and July 2011 were reviewed. Serum creatinine levels before and after coronary angiography were recorded. CIAKI was diagnosed according to an increase in serum creatinine > 0.5 mg/dL or 25% above baseline. RESULTS: A total of 1,472 subjects were included in this study. Patients taking RAS blockers were older, had a higher baseline creatinine level, lower estimated glomerular filtration rate (eGFR), and had received a greater volume of contrast medium. After propensity score matching, no difference was observed between the RAS (+) and RAS (.) groups. Multiple logistic regression identified RAS blockade, age, severe heart failure, contrast volume used, hemoglobin level, and eGFR as predictors of CIAKI. Multiple logistic regression after propensity matching showed that RAS blockade was associated with CIAKI (odds ratio, 1.552; p = 0.026). CONCLUSIONS: This study showed that the incidence of CIAKI was increased in patients treated with RAS blockers.

Análisis crítico de un artículo: La suspensión de inhibidores de la bomba de protones induciría síntomas de reflujo / Critically appraised article

Background & Aims: Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). IfRAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. Methods: A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom. Results: There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPIgroup at week 10 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .023), week 11 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .009), and week 12 (1.3 ± 1.2 vs 1.0 ± 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported >1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPIgroup was 13 of 59 (22%) at week 10,13 of59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). Conclusions: PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

Tratamento da hipertensão arterial com olmesartana medoxomila em escalonamento / Based treatment algorithm for essencial hypertension with olmesartan medoxomil

FUNDAMENTO: As diretrizes nacionais e internacionais enfatizam a importância do tratamento eficaz da hipertensão arterial. Apesar disso, verificam-se baixos índices de controle e alcance das metas preconizadas, indicando que é importante planejar e implementar melhores estratégias de tratamento. OBJETIVO: Avaliar a eficácia de um tratamento, em escalonamento de doses, tendo como base a olmesartana medoxomila. MÉTODOS: Este é um estudo aberto, nacional, multicêntrico e prospectivo, de 144 pacientes com hipertensão arterial primária nos estágios 1 e 2, virgens de tratamento ou após período de washout de duas a três semanas para aqueles em tratamento ineficaz. Avaliou-se o uso da olmesartana medoxomila num algoritmo de tratamento, em quatro fases: (i) monoterapia (20 mg), (ii-iii) associada à hidroclorotiazida (20/12,5 mg e 40/25 mg) e (iv) adição de besilato de anlodipino (40/25 mg + 5 mg). RESULTADOS: Ao fim do tratamento, em escalonamento, 86 por cento dos sujeitos de pesquisa alcançaram a meta de pressão arterial (PA) < 130/85 mmHg. Ocorreram reduções na pressão arterial sistólica (PAS) e na pressão arterial diastólica (PAD) de, no máximo, -44,4 mmHg e -20,0 mmHg, respectivamente. A taxa dos respondedores sistólicos (PAS > 20 mmHg) foi de 87,5 por cento e diastólicos (PAD > 10 mmHg) de 92,4 por cento. CONCLUSÃO: O estudo se baseou em um esquema de tratamento semelhante à abordagem terapêutica da prática clínica diária e mostrou que o uso da olmesartana medoxomila, em monoterapia ou em associação a hidroclorotiazida e anlodipino, foi eficaz para o alcance de meta para hipertensos dos estágios 1 e 2.

BACKGROUND: The national and international guidelines emphasize the importance of the effective treatment of essenssial hypertension. Nevertheless, low levels of control are observed, as well as low attainment of the recommended goals, indicating that it is important to plan and implement better treatment strategies. OBJECTIVE: To evaluate the efficacy of a based treatment algorithm with olmesartan medoxomil. METHODS: This is an open, national, multicentric and prospective study of 144 patients with primary arterial hypertension, stages 1 and 2, naïve to treatment or after a 2-to-3 week washout period for those in whom treatment was ineffective. The use of olmesartan medoxomil was assessed in a treatment algorithm divided into 4 phases: (i) monotherapy (20 mg), (ii-iii) associated to à hydrochlorothiazide (20/12.5 mg and 40/25 mg) and (iv) addition of amlodipine besylate (40/25 mg + 5 mg). RESULTS: At the end of the phased-treatment, 86 percent of the study subjects attained the goal of BP < 130/85 mmHg. Maximum reductions in SAP and DAP were -44.4 mmHg and -20.0 mmHg, respectively. The rate of systolic responders (SAP > 20 mmHg) and of diastolic responders (DAP > 10 mmHg) was 87.5 percent and 92.4 percent, respectively. CONCLUSION: The study was based on a treatment regimen that was similar to the therapeutic approach in daily clinical practice and showed that the use of olmesartan medoxomil in monotherapy or in association with hydrochlorothiazide and amlodipine was effective in the attainment of the recommended goals for hypertension stage 1 and 2 hypertensive individuals.

Efectos sobre la función renal fetal y neonatal del tratamiento con antagonista del receptor de angiotensina II en el embarazo: Caso clínico / Transient renal failure in a newborn due angiotensin receptor II antagonist use during pregnancy: Report of one case

Fetal renal structure and function can be altered by medications prescribed to pregnant women. We report a chronic hypertensive pregnant woman treated with ¡osarían before and throughout pregnancy. At 30 weeks the patient was referred to our Fetal Medicine Unit due to absent amniotic fluid with normal uterine artery Doppler and fetal growth. During her hospitalization a new scan was performed showing that both fetal kidneys were enlarged and slightly hyperechogenic and placental and fetal artery Doppler showed signs of hypovolemia or increased resistance to feto-placental blood flow. Ductus venosous was normal. The fetus was delivered after three days by caesarean section at 30+4 weeks of gestation due to abnormal fetal heart rate tracing. Following delivery, the preterm newborn was treated for a transient renal failure characterized by anuria-oliguria and high plasma creatinine levels (from 3.8 mg/dL at day 5 to 0.8 mg/dL at 16 days). At 30 days of age, ultrasound showed kidneys of normal form and size. The adverse effects of Angiotensin II receptor antagonists in fetal nephrogenesis and function are discussed

Hiperkalemia grave asociada a drogas que actúan sobre el sistema renina, angiotensina, aldosterona: Un problema que requiere atención: Caso clínico / Severe hyperkalemia associated to the use of losartan and spironolactone: Case report

Hyperkalemia is a complications of the use of angiotensin converting enzyme inhibitors, angiotensin receptor antagonists and aldosterone antagonists. These drugs are commonly used for the treatment of hypertension and cardiac failure. We report a 84 year-old female treated with losartan 50 mg/day and spironolactone 25 mg/day that presented with a hyperkalemia of 8.4 mEq/l and bradicardia, drowsiness and respiratory depression. She required hemodialysis and ventilatory assistance. She was discharged in good conditions five days after admission.

A pilot study for evaluation of the efficacy and safety of telmisartan in reducing microalbuminuria in hypertensive patients with type 2 diabetes mellitus.

To evaluate efficacy and tolerability of telmisartan, an angiotensim II receptor blocker, in reducing microalbuminuria in adult Indian hypertensive patients with type 2 diabetes mellitus, a prospective, open-label, non-comparative, assessor-blind, multicentric, pilot study was conducted in 60 eligible hypertensive patients with type 2 diabetes mellitus and microalbuminuria after obtaining their informed consent. The study was approved by the respective institutional review boards. Each patient received telmisartan 40 mg initially once daily for first 4 weeks which was titrated upwards to 80 mg once daily for the next 8 weeks. Blood pressure was assessed at the end of every 2 weeks and urinary albumin excretion and creatinine clearance were measured at baseline and after 12 weeks of therapy. Safety outcome measures included monitoring of physical examination, laboratory parameters and monitoring treatment-emergent adverse events. Fifty-five patients completed the study while 5 cases were lost to follow-up. The mean age of the patients was 48.27 years. Of the total patients 63.6% were males and 46.4% were females. At baseline the mean urinary albumin excretion rate was 131.81 +/- 38.82 mg/minute. A statistically significant (p < 0.05) reduction (32.96%) in urinary albumin excretion rate occurred after 12 weeks of therapy (118.36 +/- 37.22). The mean pre-study systolic blood pressure was 165.05 +/- 15.24 mmHg which was significantly (p < 0.05) reduced to 123.72 +/- 5.88 mmHg at the end of 12 weeks. At baseline the mean diastolic blood pressure was 103.55 +/- 9.84 mmHg which was significantly (p < 0.05) reduced to 84.71 +/- 8.54 mmHg. The JNC-VII goal of blood pressure below 130/80 was achieved in 34 (61.8%)of the 55 patients at the end of 12 weeks. Both fasting and postprandial blood sugar levels were well-controlled at the end of the study. Telmisartan was well tolerated with only 9.09% of the patients reported mild and transient adverse events like fatigue, dizziness, nausea and diarrhoea. No abnormalities were detected in the laboratory parameters. The results of this pilot study indicate that telmisartan is effective, safe and well tolerated while reducing microalbuminuria in adult Indian hypertensive patients with type 2 diabetes mellitus.